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• W2891246970 abstract "Background: Striking variability in global gallbladder cancer (GBCA) incidence suggests regional differences in pathogenesis, although distinctive, geographic-related tumor genetic mutations have not been shown. This study assesses for regional differences in GBCA pathogenesis by analyzing the mutation pattern of specimens from 3 countries (Chile, Japan, USA). Methods: Tumors and clinicopathologic data from patients treated at 3 centers between 1996 and 2016 were analyzed. Primary tumor and normal tissue underwent targeted sequencing for known cancer genes. Mutations and pathways were correlated with clinicopathologic variables and compared among sites using Fisher’s Exact and Wilcoxon Rank Sum tests. Overall survival (OS) was estimated from the time of surgery using Kaplan-Meier methods. Results: Seventy-one patients were included (Chile n = 21, Japan n = 11, USA n = 49). Japanese patients were older (median = 72y, range 54–81) vs. Chilean (m:59y, r:32–73) and American patients (m:66y, r:46–81, p = 0.002), most were male (64%, vs. Chile = 19% and USA = 39%, p = 0.048), more had well-differentiated tumors (45%, vs. Chile/USA = 0%, p = 0.001), and fewer had distant metastases (0%, vs. Chile = 76% and USA = 18%, p < 0.001). Japan had a median of 7 mutations/patient (r:0–23) vs. Chile = 9 (r:4–26) and USA = 5 (r:0–38, p = 0.006). Mutations in ARID1A and PIK3CA were notably absent from Japanese tumors, but no mutation or pathway was more prevalent among sites. SMAD4 mutation had similar presence (Chile = 38%, Japan = 36%, USA = 27%, p = 0.66) but was associated with worse OS (median 10 vs. 25 months, p = 0.032). Conclusion: Differences in clinicopathologic variables suggest a distinct pathogenesis of GBCA in Japanese patients, which may be supported by differences in mutation pattern. Among all sites, SMAD4 mutation was present in one-third of patients and was associated with worse survival." @default.
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• W2891246970 date "2018-03-01" @default.
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• W2891246970 title "Regional differences in gallbladder cancer pathogenesis: Insights from a comparison of tumor mutations" @default.
• W2891246970 doi "https://doi.org/10.1016/j.hpb.2018.02.003" @default.
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